ObjectivesTo date, there is no valuable tool to assess fibrotic disease activity in humans in vivo in a non-invasive way. This study aims to uncouple inflammatory from fibrotic disease activity in fibroinflammatory diseases such as IgG4-related disease.MethodsIn this cross-sectional clinical study, 27 patients with inflammatory, fibrotic and overlapping manifestations of IgG4-related disease underwent positron emission tomography (PET) scanning with tracers specific for fibroblast activation protein (FAP; 68Ga-FAP inhibitor (FAPI)-04), 18F-fluorodeoxyglucose (FDG), MRI and histopathological assessment. In a longitudinal approach, 18F-FDG and 68Ga-FAPI-04 PET/CT data were evaluated before and after immunosuppressive treatment and correlated to clinical and MRI data.ResultsUsing combination of 68Ga-FAPI-04 and 18F-FDG-PET, we demonstrate that non-invasive functional tracking of IgG4-related disease evolution from inflammatory towards a fibrotic outcome becomes feasible. 18F-FDG-PET positive lesions showed dense lymphoplasmacytic infiltration of IgG4+ cells in histology, while 68Ga-FAPI-04 PET positive lesions showed abundant activated fibroblasts expressing FAP according to results from RNA-sequencing of activated fibroblasts. The responsiveness of fibrotic lesions to anti-inflammatory treatment was far less pronounced than that of inflammatory lesions.ConclusionFAP-specific PET/CT permits the discrimination between inflammatory and fibrotic activity in IgG4-related disease. This finding may profoundly change the management of certain forms of immune-mediated disease, such as IgG4-related disease, as subtypes dominated by fibrosis may require different approaches to control disease progression, for example, specific antifibrotic agents rather than broad spectrum anti-inflammatory treatments such as glucocorticoids.

Low temperature fuel cells are clean, effective alternative fuel conversion technology. Oxygen reduction reaction (ORR) at the fuel cell cathode has required Pt as the electrocatalyst for high activity and selectivity of the four-electron reaction pathway. Targeting a less expensive, earth abundant alternative, we have developed the synthesis of cobalt phosphide (Co2P) nanorods for ORR. Characterization techniques that include total X-ray scattering and extended X-ray absorption fine structure revealed a deviation of the nanorods from bulk crystal structure with a contraction along the b orthorhombic lattice parameter. The carbon supported nanorods have comparable activity but are remarkably more stable than conventional Pt catalysts for the oxygen reduction reaction in alkaline environments.

The first 2000 general-use patients managed with hemodynamic-guided heart failure care had higher PA pressures at baseline and experienced greater reduction in PA pressure over time compared with the pivotal CHAMPION clinical trial. These data demonstrate that general use of implantable hemodynamic technology in a nontrial setting leads to significant lowering of PA pressures.

Structural defects and their dynamics play an important role in controlling the behavior of phase-change materials (PCM) used in low-power nonvolatile memory devices. However, not much is known about the influence of disorder on the electronic properties of crystalline PCM prior to a structural phase-change. Here, we show that the application of voltage pulses to single-crystalline GeTe nanowire memory devices introduces structural disorder in the form of dislocations and antiphase boundaries (APB). The dynamic evolution and pile-up of APBs increases disorder at a local region of the nanowire, which electronically transforms it from a metal to a dirty metal to an insulator, while still retaining single-crystalline long-range order. We also observe that close to this metal-insulator transition, precise control over the applied voltage is required to create an insulating state; otherwise the system ends up in a more disordered amorphous phase suggesting the role of electronic instabilities during the structural phase-change.